This invention is the result of work supported by the National Institute of Health, grant Nos. A112069, CA19589 and AM33713. The government has rights in the invention.
This invention relates to activation of cells involved in the immune response.
T lymphocytes play a central role in the immune response by virtue of their ability to recognize antigens with a high degree of specificity, to act as effector cells, and to regulate the nature and intensity of the immune response. The identification of specific antigens on T-cells which are involved in target cell recognition, and the availability of monoclonal antibodies which recognize such antigens, allows a detailed characterization of both the process of T-cell activation and the distinct subsets of T-cells. For example, monoclonal antibodies against the antigen-receptor complex Ti/T3 (CD3), and a combination of antibodies against epitopes on the T11 (CD2) antigen, have been found to induce the proliferation of T-cells. Another antibody, 9.3, which recognizes a distinct glycoprotein of 44,000 Daltons (D) has also been reported to stimulate cells, either alone or in conjunction with the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (PTA). In mice, several antibodies have been used to identify other T-cell stimulating antigens, such as a product of the Ly6 locus (TAP) and the thy-1 antigen.
In addition to the target recognition role of individual structures on the surface of T-cells, evidence is accumulating to support the idea of an interaction between distinct T-cell antigens in the regulation of T-cell growth. For example, antibodies against the T3/Ti complex have been reported to block T11-induced proliferation, and vice versa. Similarly, in the absence of monocytes, combinations of non-mitogenic antibodies against either the T3 and T11 antigens or the T3 and T1 (CD5) antigens have been found to cause proliferation of resting T-cells.